Lung cancer is not a single diagnosis but a collection of diseases defined by the uncontrolled growth of cells in the lungs. Modern science allows for a more detailed classification based on specific genetic profiles, moving away from a generalized treatment model toward a personalized one. By examining the genetic makeup of cancer cells, clinicians can identify the specific drivers of the disease. This allows for the development of treatments that target the distinct molecular pathways of an individual’s cancer, redefining how advanced-stage lung cancer is managed.
The Role of Genetic Mutations in Lung Cancer
Genes are segments of DNA that provide instructions for building proteins and controlling cellular functions. A mutation is a change in a gene’s DNA sequence, and while many are harmless, certain types can alter a cell’s behavior. In cancer, some mutations act like a permanently engaged “on-switch” for cell growth and division, disrupting the normal processes that keep cell proliferation in check.
These changes can cause cells to multiply uncontrollably, leading to the formation of a tumor. This process can be compared to a car’s accelerator being stuck, causing the vehicle to speed forward without restraint. The genetic mutations driving most lung cancers are “somatic,” meaning they are acquired in the lung cells during a person’s lifetime and are not inherited. Identifying these specific genetic drivers is a primary focus of modern oncology.
Common Genetic Subtypes in Non-Small Cell Lung Cancer
The majority of lung cancers are classified as Non-Small Cell Lung Cancer (NSCLC), which has several distinct genetic subtypes. The Epidermal Growth Factor Receptor (EGFR) mutation is a common example. EGFR is a protein that normally helps cells grow, but certain mutations cause it to become overactive, leading to excessive cell proliferation. These mutations are more frequently found in individuals who are light or never smokers.
Another subtype involves a rearrangement of the Anaplastic Lymphoma Kinase (ALK) gene. In this situation, a piece of the ALK gene breaks off and fuses with another gene, creating an abnormal “fusion protein” that constantly signals the cancer cell to grow. Similar mechanisms are seen in ROS1 and RET rearrangements, which also result in fusion proteins that promote tumor development. These rearrangements are mutually exclusive, meaning a tumor will have one, but not multiple, of these specific changes.
The Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) mutation is one of the most frequently identified genetic alterations in NSCLC, present in about a quarter of adenocarcinomas. Another mutation, BRAF, is also found in a subset of lung cancers and is notable for its presence in other cancers, such as melanoma. Identifying which of these specific genetic subtypes is present in a tumor is a standard part of the diagnostic process.
The Process of Biomarker Testing
Identifying a lung cancer’s genetic subtype is accomplished through biomarker testing, also known as molecular profiling. This analysis looks for specific genes, proteins, or other substances that can provide information about the cancer. The traditional method for obtaining the necessary material is a tissue biopsy, where a small sample of the tumor is surgically removed for laboratory analysis.
A less invasive method is the liquid biopsy. This technique involves a simple blood draw to detect circulating tumor DNA (ctDNA), which is genetic material shed from the tumor into the bloodstream. This approach is useful when a tissue biopsy is difficult to perform or to monitor the cancer’s genetic changes over time.
In the laboratory, the tumor sample is often analyzed using Next-Generation Sequencing (NGS). NGS is a powerful method that allows technicians to rapidly sequence large amounts of DNA. This makes it possible to test for numerous genetic mutations simultaneously from a single sample, providing a detailed molecular blueprint of the tumor.
Connecting Subtypes to Targeted Therapies
The primary reason for biomarker testing is to match a patient’s genetic subtype to an appropriate targeted therapy. These medications are designed to interfere with the specific molecules involved in cancer growth. Because they act on the precise mechanisms driving the cancer, these therapies can be highly effective and may have fewer side effects than traditional chemotherapy, which affects all rapidly dividing cells, both cancerous and healthy.
For instance, an EGFR mutation is treated with EGFR inhibitors, which block the signals from the mutated protein. Patients with an ALK or ROS1 rearrangement receive specific inhibitors to block the activity of the abnormal fusion proteins. The development of specific KRAS inhibitors has also provided an effective treatment option for patients with this common subtype. This allows for a personalized treatment strategy tailored to the unique molecular characteristics of a tumor.